cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2454cardio-236Research ArticleОБЗОРЫREVIEWSОптимизация дигиталисной терапии в клинической практикеOptimization of digitalis therapy in clinical practiceДядыкА. И.DyadykA. I.noemail@neicon.ruЕфременкоВ. А.EfremenkoV. A.noemail@neicon.ruКуглерТ. Е.KuglerT. E.noemail@neicon.ruМальцеваН. В.MaltsevaN. V.noemail@neicon.ruПриколотаО. А.PrykolotaO. A.noemail@neicon.ru«ДонНМУ им. М. Горького»РоссияM. Gorky Donetsk National Medical UniversityRussian Federation201818112018585S1319Copyright © Kardiomag, 20182018KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/236

В последние годы наблюдается отчетливое снижение частоты применения дигиталисных препаратов у больных с СН при синусовом ритме и фибрилляции предсердий. Результаты опубликованных исследований часто противоречат друг другу. Одни из них ставят под сомнение благоприятный эффект дигоксина у больных с СН, другие опровергают увеличение летальности и частоты госпитализаций, ассоциированных с применением дигоксина. В связи с этим мы сочли важным беспристрастно проанализировать эти сообщения и отразить современные взгляды на механизмы действия сердечных гликозидов, особенности фармакокинетики и возможности оптимизации дигиталисной терапии в кардиологической практике.

In recent years there has been a marked decrease in cardiac glycosides use in patients with heart failure in sinus rhythm and atrial fibrillation. The results of published studies contradict each other. Some of them doubt the favorable effect of digoxin in patients with heart failure; others refute the increase in the lethality and frequency of hospitalizations associated with the use of digoxin. In this regard, we found it important to analyze these reports impartially and reflect modern views on the mechanisms of cardiac glycosides, the pharmacokinetics and the possibility of optimizing digitalis therapy in cardiac practice.

сердечные гликозидыдигиталисные препаратыдигоксинсердечная недостаточностьфибрилляция предсердийлетальностьчастота госпитализацийcardiac glycosidesdigitalisdigoxinheart failureatrial fibrillationlethalityhospitalizationsReferencesWithering W. An account of the foxglove, and some ofits medical uses: with practical remarks on dropsy, and other diseases/by William Withering. [Internet]. -Birmingham: Printed by M. Swinney for G. G. J. and J. Robinson. London., 1785Withering W. An account of the foxglove, and some ofits medical uses: with practical remarks on dropsy, and other diseases/by William Withering. [Internet]. -Birmingham: Printed by M. Swinney for G. G. J. and J. Robinson. London., 1785Дядык А. И. Место сердечных гликозидов в клинической практике: дискуссии продолжаются. -Донецк, 2016. 180 p.Дядык А. И. Место сердечных гликозидов в клинической практике: дискуссии продолжаются. -Донецк, 2016. 180 p.Дядык А. И., Багрий А. Э. Сердечные гликозиды. Донецк. -Донбасс, 2000. 300 p.Дядык А. И., Багрий А. Э. Сердечные гликозиды. Донецк. -Донбасс, 2000. 300 p.Drugs in Cardiology: A Comprehensive Guide to Cardiovascular Pharmacotherapy [Internet]. Kaski JC, Hayward C., Mahida S., Baker S., Khong T., Tamargo J., editors. 0xford University Press, 2010Nov [cited 2018]. ISBN: 978-0-19-955746-2Drugs in Cardiology: A Comprehensive Guide to Cardiovascular Pharmacotherapy [Internet]. Kaski JC, Hayward C., Mahida S., Baker S., Khong T., Tamargo J., editors. 0xford University Press, 2010Nov [cited 2018]. ISBN: 978-0-19-955746-2Hosenpud JD, Greenberg BH. Congestive Heart Failure: Pathophysiology, Diagnosis, and Comprehensive Approach to Management. [Internet]. - New York: Springer New York, 1994 [cited 2018]. ISBN: 978-1-4613-8315-4Hosenpud JD, Greenberg BH. Congestive Heart Failure: Pathophysiology, Diagnosis, and Comprehensive Approach to Management. [Internet]. - New York: Springer New York, 1994 [cited 2018]. ISBN: 978-1-4613-8315-4Braunwald's heart disease: a textbook of cardiovascular medicine. Tenth edition. Mann DL, Zipes DP, Libby P., Bonow R0, Braunwald E., editors. - Philadelphia, PA: Elsevier/Saunders, 2015. ISBN: 978-1-4557-5134-1Braunwald's heart disease: a textbook of cardiovascular medicine. Tenth edition. Mann DL, Zipes DP, Libby P., Bonow R0, Braunwald E., editors. - Philadelphia, PA: Elsevier/Saunders, 2015. ISBN: 978-1-4557-5134-1Drugs for the heart. 8th ed. 0pie LH, Gersh BJ, editors. - Philadelphia, PA: Elsevier Saunders, 2013. 573 p. ISBN: 978-1-4557-3322-4Drugs for the heart. 8th ed. 0pie LH, Gersh BJ, editors. - Philadelphia, PA: Elsevier Saunders, 2013. 573 p. ISBN: 978-1-4557-3322-4Mackenzie J. Digitalis. Heart. 1911. 273-389 p.Mackenzie J. Digitalis. Heart. 1911. 273-389 p.Hauptman PJ, Kelly R.A. Digitalis. Circulation. 1999,99 (9):1265-70. PMID:10069797Hauptman PJ, Kelly R.A. Digitalis. Circulation. 1999,99 (9):1265-70. PMID:10069797Katz A., Lifshitz Y., Bab-Dinitz E., Kapri-Pardes E., Goldshleger R., Tal DM, et al. Selectivity of Digitalis Glycosides for Isoforms of Human Na, K-ATPase.Journal of Biological Chemistry. 2010,285 (25):19582-92. D0I:10.1074/jbc. M110.119248Katz A., Lifshitz Y., Bab-Dinitz E., Kapri-Pardes E., Goldshleger R., Tal DM, et al. Selectivity of Digitalis Glycosides for Isoforms of Human Na, K-ATPase.Journal of Biological Chemistry. 2010,285 (25):19582-92. D0I:10.1074/jbc. M110.119248Гуревич А. М., Гаврилин А. А. Сердечные гликозиды в современной клинической практике. Альманах Клинической Медицины. 2014, (35):101-5Гуревич А. М., Гаврилин А. А. Сердечные гликозиды в современной клинической практике. Альманах Клинической Медицины. 2014, (35):101-5Беловол А. Н., Князькова И. И. Клиническая фармакология сердечных гликозидов. Новости медицины и фармации. 2012, (3 (401)): 12-4.Беловол А. Н., Князькова И. И. Клиническая фармакология сердечных гликозидов. Новости медицины и фармации. 2012, (3 (401)): 12-4.Heart failure in clinical practice. 2nd ed. MacMurray JJV, Cleland JGF, editors. - London: Dunitz, 2000. 343 p. ISBN: 978-1-85317-561-9Heart failure in clinical practice. 2nd ed. MacMurray JJV, Cleland JGF, editors. - London: Dunitz, 2000. 343 p. ISBN: 978-1-85317-561-9Pervaiz MH, Dickinson MG, Yamani M. Is digoxin a drug of the past? Cleve Clin J. Med. 2006,73 (9):821-4, 826, 829-832 passim. PMID:16970134Pervaiz MH, Dickinson MG, Yamani M. Is digoxin a drug of the past? Cleve Clin J. Med. 2006,73 (9):821-4, 826, 829-832 passim. PMID:16970134Cleland JGF, Cullington D. Digoxin: Quo Vadis? Circulation: Heart Failure. 2009,2 (2):81-5. D01:10.1161/CIRCHEARTFAILURE. 109.859322Cleland JGF, Cullington D. Digoxin: Quo Vadis? Circulation: Heart Failure. 2009,2 (2):81-5. D01:10.1161/CIRCHEARTFAILURE. 109.859322Guyatt GH, Sullivan MJ, Fallen EL, Tihal H., Rideout E., Halcrow S. et al. A controlled trial of digoxin in congestive heart failure. Am J. Cardi ol. 1988,61 (4):371-5. PMID:3277366Guyatt GH, Sullivan MJ, Fallen EL, Tihal H., Rideout E., Halcrow S. et al. A controlled trial of digoxin in congestive heart failure. Am J. Cardi ol. 1988,61 (4):371-5. PMID:3277366Juillière Y., Selton-Suty C. Digoxin therapy: A persisting interest despite contrary winds. Archives of Cardiovascular Diseases. 2010,103 (5):281-4. D0I:10.1016/j. acvd. 2010.04.001Juillière Y., Selton-Suty C. Digoxin therapy: A persisting interest despite contrary winds. Archives of Cardiovascular Diseases. 2010,103 (5):281-4. D0I:10.1016/j. acvd. 2010.04.001Chan KE, Lazarus JM, Hakim R.M. Digoxin Associates with Mortality in ESRD. Journal of the American Society of Nephrology. 2010,21 (9):1550-9.D0I:10.1681/ASN. 2009101047Chan KE, Lazarus JM, Hakim R.M. Digoxin Associates with Mortality in ESRD. Journal of the American Society of Nephrology. 2010,21 (9):1550-9.D0I:10.1681/ASN. 2009101047Damman K., Tang WHW, Felker GM, Lassus J., Zannad F., Krum H. et al. Current Evidence on Treatment ofPatients With Chronic Systolic Heart Failure and Renal Insufficiency.Journal of the American College of Cardiology. 2014,63 (9):853-71. D0I:10.1016/j. jacc. 2013.11.031Damman K., Tang WHW, Felker GM, Lassus J., Zannad F., Krum H. et al. Current Evidence on Treatment ofPatients With Chronic Systolic Heart Failure and Renal Insufficiency.Journal of the American College of Cardiology. 2014,63 (9):853-71. D0I:10.1016/j. jacc. 2013.11.031Gheorghiade M. Contemporary Use of Digoxin in the Management of Cardiovascular Disorders. Circulation. 2006,113 (21):2556-64. D0I:10.1161/ CIRCULATI0NAHA. 105.560110Gheorghiade M. Contemporary Use of Digoxin in the Management of Cardiovascular Disorders. Circulation. 2006,113 (21):2556-64. D0I:10.1161/ CIRCULATI0NAHA. 105.560110Goldberger ZD, Alexander GC. Digitalis Use in Contemporary Clinical Practice: Refitting the Foxglove. JAMA Internal Medicine. 2014,174 (1):151. D0I:10.1001/jamainternmed. 2013.10432Goldberger ZD, Alexander GC. Digitalis Use in Contemporary Clinical Practice: Refitting the Foxglove. JAMA Internal Medicine. 2014,174 (1):151. D0I:10.1001/jamainternmed. 2013.10432Kotecha D., Holmes J., Krum H., Altman DG, Manzano L., Cleland JGF, et al. Efficacy of ß blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. RAe Lancet. 2014,384 (9961):2235-43. D0I:10.1016/S0140-6736 (14) 61373-8Kotecha D., Holmes J., Krum H., Altman DG, Manzano L., Cleland JGF, et al. Efficacy of ß blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. RAe Lancet. 2014,384 (9961):2235-43. D0I:10.1016/S0140-6736 (14) 61373-8Washam JB, Stevens SR, Lokhnygina Y., Halperin JL, Breithardt G., Singer DE et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban 0nce Daily 0ral Direct Factor Xa Inhibition Compared with Vitamin K. Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (R0CKET AF). RAe Lancet. 2015,385 (9985):2363-70. D01:10.1016/S0140-6736 (14) 61836-5Washam JB, Stevens SR, Lokhnygina Y., Halperin JL, Breithardt G., Singer DE et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban 0nce Daily 0ral Direct Factor Xa Inhibition Compared with Vitamin K. Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (R0CKET AF). RAe Lancet. 2015,385 (9985):2363-70. D01:10.1016/S0140-6736 (14) 61836-5Сулимов В. А., Голицын С. П., Панченко Е. П., Попов С. В., Ревишвили А. Ш., Шубик Ю. В. и др. Диагностика и лечение фибрилляций предсердий. Рекомендации РКО, ВНОА И. АССХ. Российский кардиологический журнал. 2013,4 S3:1-100.Сулимов В. А., Голицын С. П., Панченко Е. П., Попов С. В., Ревишвили А. Ш., Шубик Ю. В. и др. Диагностика и лечение фибрилляций предсердий. Рекомендации РКО, ВНОА И. АССХ. Российский кардиологический журнал. 2013,4 S3:1-100.Мареев В. Ю., Агеев Ф. Т., Арутюнов Г. П., Коротеев А. В., Мареев Ю. В., Овчинников А. Г. и др. Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению ХСН (четвертый пересмотр). Утверждены на Конгрессе ОССН 7 декабря 2012 года, на Правлении ОССН 31 марта 2013 и Конгрессе РКО 25 сентября 2013 года. Журнал Сердечная Недостаточность. 2013,14 (7):379-472Мареев В. Ю., Агеев Ф. Т., Арутюнов Г. П., Коротеев А. В., Мареев Ю. В., Овчинников А. Г. и др. Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению ХСН (четвертый пересмотр). Утверждены на Конгрессе ОССН 7 декабря 2012 года, на Правлении ОССН 31 марта 2013 и Конгрессе РКО 25 сентября 2013 года. Журнал Сердечная Недостаточность. 2013,14 (7):379-472January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014,130 (23):e199-267. D01:10.1161/CIR. 0000000000000041January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014,130 (23):e199-267. D01:10.1161/CIR. 0000000000000041Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017,136 (6):e137-61. DOI:10.1161/CIR. 0000000000000509Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017,136 (6):e137-61. DOI:10.1161/CIR. 0000000000000509Kirchhof P., Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016,37 (38):2893-962.DOI:10.1093/eurheartj/ehw210Kirchhof P., Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal. 2016,37 (38):2893-962.DOI:10.1093/eurheartj/ehw210Ponikowski P., Voors AA, Anker SD, Bueno H., Cleland JGF, Coats AJS et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016,37 (27):2129-200. DOI:10.1093/eurheartj /ehw128Ponikowski P., Voors AA, Anker SD, Bueno H., Cleland JGF, Coats AJS et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016,37 (27):2129-200. DOI:10.1093/eurheartj /ehw128Cleland J., Pennell D., Ray S., Coats A., Macfarlane P., Murray G. et al. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. The Lancet. 2003,362 (9377):14-21. DOI:10.1016/S0140-6736 (03) 13801-9Cleland J., Pennell D., Ray S., Coats A., Macfarlane P., Murray G. et al. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. The Lancet. 2003,362 (9377):14-21. DOI:10.1016/S0140-6736 (03) 13801-9Flather MD, Shibata MC, Coats AJS, Van Veldhuisen DJ, Parkhomenko A., Borbola J. et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). European Heart Journal. 2005,26 (3):215-25. DOI:10.1093/eurheartj/ehi115Flather MD, Shibata MC, Coats AJS, Van Veldhuisen DJ, Parkhomenko A., Borbola J. et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). European Heart Journal. 2005,26 (3):215-25. DOI:10.1093/eurheartj/ehi115Шарипова А. Р. Фармакологические свойства сердечных гликозидов. Science Time. 2016, (12 (36)): 776-9.Шарипова А. Р. Фармакологические свойства сердечных гликозидов. Science Time. 2016, (12 (36)): 776-9.Zhao L., Yang P., Li P., Wang X., Qin W., Xianglin Z. Efficiency of individual dosage of digoxin with calculated concentration. Clinical Interventions in Aging. 2014,1205. DOI:10.2147/CIA. S63596Zhao L., Yang P., Li P., Wang X., Qin W., Xianglin Z. Efficiency of individual dosage of digoxin with calculated concentration. Clinical Interventions in Aging. 2014,1205. DOI:10.2147/CIA. S63596Пушкин А. С., Яковлев А. А., Задворьев С. Ф., Рукавишникова С. А., Ахмедов Т. А. Дигоксин у пациентов старших возрастных групп: терапевтический мониторинг как способ повышения эффективности терапии (обзор). Успехи Геронтологии. 2016, (2):297-305.Пушкин А. С., Яковлев А. А., Задворьев С. Ф., Рукавишникова С. А., Ахмедов Т. А. Дигоксин у пациентов старших возрастных групп: терапевтический мониторинг как способ повышения эффективности терапии (обзор). Успехи Геронтологии. 2016, (2):297-305.Cardiology: fundamentals and practice. Brandenburg RO, editor. - Chicago: Year Book Medical Publishers, 1987. 2055 p. ISBN: 978-0-8151-3495-4Cardiology: fundamentals and practice. Brandenburg RO, editor. - Chicago: Year Book Medical Publishers, 1987. 2055 p. ISBN: 978-0-8151-3495-4Gheorghiade M., Hall VB, Jacobsen G., Alam M., Rosman H., Goldstein S. Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. Circulation. 1995,92 (7):1801-7. PMID:7671364Gheorghiade M., Hall VB, Jacobsen G., Alam M., Rosman H., Goldstein S. Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. Circulation. 1995,92 (7):1801-7. PMID:7671364Slatton ML, Irani WN, Hall SA, Marcoux LG, Page RL, Grayburn PA et al. Does Digoxin Provide Additional Hemodynamic and Autonomic Benefit at Higher Doses in Patients With Mild to Moderate Heart Failure and Normal Sinus Rhythm? Journal of the American College of Cardiology. 1997,29 (6):1206-13. DOI:10.1016/S0735-1097 (97) 00057-0Slatton ML, Irani WN, Hall SA, Marcoux LG, Page RL, Grayburn PA et al. Does Digoxin Provide Additional Hemodynamic and Autonomic Benefit at Higher Doses in Patients With Mild to Moderate Heart Failure and Normal Sinus Rhythm? Journal of the American College of Cardiology. 1997,29 (6):1206-13. DOI:10.1016/S0735-1097 (97) 00057-0The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure. New England Journal of Medicine. 1997,336 (8):525-33. DOI:10.1056/NEJM199702203360801The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure. New England Journal of Medicine. 1997,336 (8):525-33. DOI:10.1056/NEJM199702203360801Packer M. End of the Oldest Controversy in Medicine - Are We Ready to Conclude the Debate on Digitalis? New England Journal of Medicine. 1997,336 (8):575-6. DOI:10.1056/NEJM199702203360809Packer M. End of the Oldest Controversy in Medicine - Are We Ready to Conclude the Debate on Digitalis? New England Journal of Medicine. 1997,336 (8):575-6. DOI:10.1056/NEJM199702203360809Rathore SS, Curtis JP, Wang Y., Bristow MR, Krumholz H.M. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003,289 (7):871-8. DOI:10.1001/jama. 289.7.871Rathore SS, Curtis JP, Wang Y., Bristow MR, Krumholz H.M. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003,289 (7):871-8. DOI:10.1001/jama. 289.7.871Goldberger ZD, Goldberger A.L. Therapeutic Ranges of Serum Digoxin Concentrations in Patients With Heart Failure. The American Journal of Cardiology. 2012,109 (12):1818-21. DOI:10.1016/j.amjcard.2012.02.028Goldberger ZD, Goldberger A.L. Therapeutic Ranges of Serum Digoxin Concentrations in Patients With Heart Failure. The American Journal of Cardiology. 2012,109 (12):1818-21. DOI:10.1016/j.amjcard.2012.02.028

The authors declare that there are no conflicts of interest present.